The purpose of this application is to request NCCR SIG funding for a VectraTM slide scanning system to be housed in the Translational Research Laboratory (TRL) in the Center for Clinical and Translational Research at the Dana-Farber Cancer Institute (DFCI). Designed as an engine for translation, moving science from the bench to the bedside and more important the bedside to the bench, the TRL by nature collaborates with many scientists across the institute and the Harvard Medical School community. The system requested has state of the art imaging and software that optimizes information from IHC, IF, HC, FISH and allows multiplexing with all these methods. For cancer research where patient solid tumor samples are difficult to obtain, multispectral analysis offers the possibilities for multiplexing that are impossible with standard RGB system. Most pressing for the TRL is the ability to analyze the rare circulating tumor cells that we capture with antibodies conjugated to magnetic particles. The VectraTM slide scanning system will facilitate the continuing mission of the TRL to make available to DFCI clinical investigators and their collaborators minimally invasive methods to detect, monitor and evaluate patient cancer by sampling and imaging cells shed into the circulation by the solid tumor. The advanced imaging provided by this system will make it possible to routinely detect key chromosomal aberrations that are linked to resistance to targeted agents, evaluate signal transduction and protein expression in response to targeted drugs and monitor overall tumor burden all from the same sample. This multiplexing is required because circulating tumors cells are rare and a single blood draw can yield as few as 10 cells. The ability to monitor the disease in this fashion is essential for understanding the biologic basis for drug resistance mechanisms and identifying appropriate patients for treatment. This will facilitate drug discovery efforts and understanding how to best use targeted cancer therapeutics. The TRL works with preclinical scientists to discover and validate pharmacodynamic markers. Kwok- Kin Wong MD PhD has developed genetically engineered mice that spontaneously form lung tumors. Charles Stiles PhD has found a pathway that makes the rare populations of brain tumor stem cells resistant to genotoxic agents. The multispectral imaging allows quantitative analysis of theses tumor samples, and the multiplexed analysis of rare subsets of tumor stem cells. In addition, the sophisticated learning software puts the power of pathologists in the hands of basic scientists. The grant describes the capabilities of the VectraTM slide scanning system and how the instrument would enhance the overall quality and efficiency of clinical and translational researcher investigations and lead to tangible reduction in the suffering caused by the cancer scourge.